dc.contributor.advisor |
Hunter, Roger |
en_ZA |
dc.contributor.author |
Cozett, Rudy Edgar
|
en_ZA |
dc.date.accessioned |
2016-01-26T12:06:47Z |
|
dc.date.available |
2016-01-26T12:06:47Z |
|
dc.date.issued |
2015 |
en_ZA |
dc.identifier.citation |
Cozett, R. 2015. Studies on the use of peptide auxiliaries in the meso-desymmetrization of epoxides, and the kinetic resolution of secondary alcohols. University of Cape Town. |
en_ZA |
dc.identifier.uri |
http://hdl.handle.net/11427/16573
|
|
dc.description |
Includes bibliographical references |
en_ZA |
dc.description.abstract |
This thesis reports on the use of amino acids and peptides as chiral ligands/catalysts in two asymmetric processes: Meso-desymmetrization of an epoxide and the kinetic resolution of secondary alcohols. Chapter 1 comprises a literature review, which gives a general overview of methods of asymmetric synthesis, followed by an overview on the existing classes of asymmetric DMAP-type acyl-transfer catalysis as the major topic of the thesis. Chapter 2 describes the synthesis and evaluation of four peptide ligands used in combination with scandium(III) triflate for the meso-desymmetrization of cyclohexene oxide. Enantioselectivities were determined by chiral HPLC, and gave results of up to 41 % ee. Chapter 3 discusses the synthesis and characterisation of three clas ses of nucleophilic DMAP-type catalysts, in which various amino acid/peptide auxiliaries were attached either α, β, or γ-to the pyridine nitrogen. The peptides contained tryptophan, chosen to exploit a potential π - π stacking interaction with the acyl-pyridinium cation. Catalysts substituted at the α and γ positions gave no kinetic resolution for 1-(2-naphthyl)ethanol 121 ; however, a dipeptide (Leu-Trp)-containing catalyst 128 substituted at the β-position gave an s-v alue of 5.3. In order to improve the selectivity, 128 was derivatised at the C-terminal to form two tripeptide-containing catalysts, and acylated at the NH group of the indole ring (141). A range of secondary alcohols were tested and selectivity factors in creased to up to 10.7 . A series of second-generation catalysts were synthesised, but s-values did not improve. An NMR study was performed to reveal a possible conformational change during the stereoselective step. Computational modelling was performed using molecular mechanics (MMFF94) and quantum mechanics (B3LYP/6-31G, M06/6-31G*, ω B97X-D/6-31G) to determine a po ssible transition-state model, which indicated a π - cation interaction of the electron-rich indole ring of a tryptophan moiety with the electron-deficient pyridinium cation as a likely determinant of stereoselectivity. |
en_ZA |
dc.language.iso |
eng |
en_ZA |
dc.subject.other |
Chemistry |
en_ZA |
dc.title |
Studies on the use of peptide auxiliaries in the meso-desymmetrization of epoxides, and the kinetic resolution of secondary alcohols |
en_ZA |
dc.type |
Doctoral Thesis |
|
uct.type.publication |
Research |
en_ZA |
uct.type.resource |
Thesis
|
en_ZA |
dc.publisher.institution |
University of Cape Town |
|
dc.publisher.faculty |
Faculty of Science |
en_ZA |
dc.publisher.department |
Department of Chemistry |
en_ZA |
dc.type.qualificationlevel |
Doctoral |
|
dc.type.qualificationname |
PhD |
en_ZA |
uct.type.filetype |
Text |
|
uct.type.filetype |
Image |
|
dc.identifier.apacitation |
Cozett, R. E. (2015). <i>Studies on the use of peptide auxiliaries in the meso-desymmetrization of epoxides, and the kinetic resolution of secondary alcohols</i>. (Thesis). University of Cape Town ,Faculty of Science ,Department of Chemistry. Retrieved from http://hdl.handle.net/11427/16573 |
en_ZA |
dc.identifier.chicagocitation |
Cozett, Rudy Edgar. <i>"Studies on the use of peptide auxiliaries in the meso-desymmetrization of epoxides, and the kinetic resolution of secondary alcohols."</i> Thesis., University of Cape Town ,Faculty of Science ,Department of Chemistry, 2015. http://hdl.handle.net/11427/16573 |
en_ZA |
dc.identifier.vancouvercitation |
Cozett RE. Studies on the use of peptide auxiliaries in the meso-desymmetrization of epoxides, and the kinetic resolution of secondary alcohols. [Thesis]. University of Cape Town ,Faculty of Science ,Department of Chemistry, 2015 [cited yyyy month dd]. Available from: http://hdl.handle.net/11427/16573 |
en_ZA |
dc.identifier.ris |
TY - Thesis / Dissertation
AU - Cozett, Rudy Edgar
AB - This thesis reports on the use of amino acids and peptides as chiral ligands/catalysts in two asymmetric processes: Meso-desymmetrization of an epoxide and the kinetic resolution of secondary alcohols. Chapter 1 comprises a literature review, which gives a general overview of methods of asymmetric synthesis, followed by an overview on the existing classes of asymmetric DMAP-type acyl-transfer catalysis as the major topic of the thesis. Chapter 2 describes the synthesis and evaluation of four peptide ligands used in combination with scandium(III) triflate for the meso-desymmetrization of cyclohexene oxide. Enantioselectivities were determined by chiral HPLC, and gave results of up to 41 % ee. Chapter 3 discusses the synthesis and characterisation of three clas ses of nucleophilic DMAP-type catalysts, in which various amino acid/peptide auxiliaries were attached either α, β, or γ-to the pyridine nitrogen. The peptides contained tryptophan, chosen to exploit a potential π - π stacking interaction with the acyl-pyridinium cation. Catalysts substituted at the α and γ positions gave no kinetic resolution for 1-(2-naphthyl)ethanol 121 ; however, a dipeptide (Leu-Trp)-containing catalyst 128 substituted at the β-position gave an s-v alue of 5.3. In order to improve the selectivity, 128 was derivatised at the C-terminal to form two tripeptide-containing catalysts, and acylated at the NH group of the indole ring (141). A range of secondary alcohols were tested and selectivity factors in creased to up to 10.7 . A series of second-generation catalysts were synthesised, but s-values did not improve. An NMR study was performed to reveal a possible conformational change during the stereoselective step. Computational modelling was performed using molecular mechanics (MMFF94) and quantum mechanics (B3LYP/6-31G, M06/6-31G*, ω B97X-D/6-31G) to determine a po ssible transition-state model, which indicated a π - cation interaction of the electron-rich indole ring of a tryptophan moiety with the electron-deficient pyridinium cation as a likely determinant of stereoselectivity.
DA - 2015
DB - OpenUCT
DP - University of Cape Town
LK - https://open.uct.ac.za
PB - University of Cape Town
PY - 2015
T1 - Studies on the use of peptide auxiliaries in the meso-desymmetrization of epoxides, and the kinetic resolution of secondary alcohols
TI - Studies on the use of peptide auxiliaries in the meso-desymmetrization of epoxides, and the kinetic resolution of secondary alcohols
UR - http://hdl.handle.net/11427/16573
ER -
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en_ZA |